Our long term objective is to understand how genes control the morphological specialization of body segments in Drosophila. A central role in this process is played by the genes of the bithorax complex (BX-C), a cluster of at least 12 genes that are thought to directly control the fates of the third thoracic and all abdominal and genital segments. Most of the research described in this application is directed toward understanding how the BX-C is organized and how its genes are controlled so that they come to be expressed in a segment specific pattern. To further define the organization of the complex, a study of the effects on segmentation of a large number of partial BX-C deletions recovered in previous work is proposed. These studies will allow a more precise mapping of BX-C genes than is now available and should reveal the degree to which the functioning of each BX-C gene is dependent upon its neighbors in the complex. To investigate how the BX-C genes are regulated, molecular studies of two genes that are required for normal spatial control of the BX-C in early development are proposed. Experiments are proposed to test our model for how one of these genes [fushi tarazu (ftz)] could control BX-C functions and to determine the nucleotide sequence changes responsible for four unusual alleles of ftz that cause defective BX-C expression. In addition, the molecular cloning and characterization of l(4)29, a gene that is expressed maternally and is required for the normal repression of BX-C functions in anterior segments, is proposed. The molecular cloning and characterization of the aristapedia (ssa) gene, which is required to prevent leg development in the distal antenna, is also planned. The analysis of ssa will include a test of the hypothesis that ss+ functions as a repressor of Antp+ in the antenna. Finally, genetic and developmental studies are proposed to characterize genes that function in the zygote to control dorsoventral differentiation. Since the mechanisms by which genes control the differentiation of body regions in Drosophila may be similar to those used in human development, the health significance of the proposed research is that it may provide a better understanding of human embryogenesis and, therefore, of certain types of congenital abnormality.